A. Field of Invention
The present invention provides an improved process for the preparation of the compound of formula I and its pharmaceutically acceptable salts or solvates thereof, which is useful as an antiviral agent.

B. Description of the Related Art
Ledipasvir is chemically known as Methyl [(2S)-1-{(6S)-6-[5-(9,9-difluoro-7{2-[(1R,3S,4S)-2-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-2azabicyclo[2.2.1]hept-3-yl]-1H-benzimidazol-6-yl)}-9H-fluoren-2-yl)-1H-imidazol-2-yl]-5azaspiro[2.4]hept-5-yl}-3-methyl-1-oxobutan-2-yl]carbamate. Ledipasvir is a hepatitis C virus (HCV) NS5A inhibitor. Ledipasvir is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection in adults (1) and it is marketed under the brand name HARVONI®.
The present disclosure relates generally to the field of an improved process for the preparation of formula (I). Hepatitis C is recognized as a chronic viral disease of the liver which is characterized by liver disease. Although drugs targeting the liver are in wide use and have shown effectiveness, toxicity and other side effects have limited their usefulness. Inhibitors of hepatitis C virus (HCV) are useful to limit the establishment and progression of infection by HCV as well as in diagnostic assays for HCV.
Ledipasvir and its pharmaceutical acceptable salts are first disclosed in U.S. Pat. No. 8,088,368 B2, and its process for the preparation discloses as 2,7-dibromo-fluoren-9-one (II) is reacted with deoxofluor to produce 2,7-dibromo-9,9-difluoro-9H-fluorene (III). The compound of formula (III) is condensed with N-Cbz-4-cyclopropyl (L) proline in presence of Pd catalyst and ethoxyvinyltributyl tin and DIEA to produce the compound of formula (IV). The compound of formula (IV) is cyclized in presence of m-xylene/ammonium acetate to produce the compound of formula (V), Further it is condensed with 2-(L)-methoxycarbonylamino-3-butyric acid (VI) in presence of DIEA in HATU and solvent to produce the compound of formula (VII). The compound of formula (VII) is condensed with compound of formula (VIII) in presence of Pd catalyst and base to produce the compound of formula (IX). Finally the compound of formula (IX) is coupled with methoxy carbonyl L-valine of formula (VI) in presence of DIEA in HATU and solvent to produce the compound of formula (I).
The above process is schematically as shown in below:

U.S. Pat. No. 9,056,860 B2 also discloses a process for the preparation of the compound of formula (I) comprising the step of condensing the compound of formula (V) with the compound of formula (VIII) in presence of PdCl2 [P (t-Bu)2Ph]2 or palladium acetate and base to produce the compound of formula (III), followed by deprotection to produce the compound of formula (IV). Finally the compound of formula (IV) is coupled with carbonyl L-valine of formula (VI) to produce the compound of formula (I).
The above process is schematically as shown in below

WO 2013/184698 A1 discloses amorphous and various crystalline forms of the compound of formula (I) and its salts or solvates thereof. This disclosure also provides a process for the preparation of making the amorphous form and crystalline forms and methods for using them in the treatment of HCV.
The major disadvantage with the above prior art process is its use of expensive catalysts and large amounts of solvents. Additionally, the yield of the prior art process is diminished by the large amount of by-products and impurities. Therefore, the prior art process for preparing Ledipasvir is not optimal for industrial scale production.
Hence, there is consequently a need for an improved method for the preparation of Ledipasvir and its intermediates which does not involve the problems described above. Some embodiments of the present invention may provide one or more benefits or advantages over the prior art.